The brain's potential to flexibly engage different functional networks in a rapidly changing environment is crucial both for facilitating a wide variety of behaviors and adaptively reorganizing following damage. This network plasticity can emerge through both changes in the local connectivity strengths within functional networks and the more global network structure of the whole brain. A recent surge of studies has assessed the intrinsic functional connectivity of local networks of brain regions during rest using functionl MRI (fMRI). Quantifying the global properties of this complex brain organization is now possible using graph theoretical tools, in which brain regions are defined as nodes and connections between regions are defined as edges. The broad goal of this proposal is to apply local, network-specific connectivity measurements as well as global, graph theoretical methods to examine the capacity for neuroplasticity under two different contexts: disruption of cortical function (acute and chronic) and specific cognitive task demands. Studies of the effect of brain damage on network organization have focused on the local, network specific effects of damage, generally finding that damage to one portion of a network effects connected but undamaged regions. The consequence of focal damage on global brain organization has primarily been examined with simulated lesion data and it is proposed that brain regions particularly important for integrating information across networks, are most critical to maintaining network integrity. Here we will test this prediction by using resting state fMRI data collected from patients with focal brain lesions and healthy participants following transcranial magnetic stimulation (TMS). We will test the hypothesis that perturbation of intrinsic brain organization results in both local decreases in the affected network and global reconfiguration of brain modules. Moreover, we hypothesize that the roles of nodes within networks that have reconfigured following brain damage is compensatory. Another approach for investigating network reconfiguration is to compare brain organization at rest to that during a cognitive task. Thus, we will also test the hypothesis that, similar to the adaptive reorganization after damage, specific task demands will result in rapid alteration of network organization at both the global and local level. This proposa will further knowledge about brain organization and its potential for plasticity in various context, such as brain damage and the dynamics cognitive demands of daily life. Moreover, we propose that network approaches such as those applied in this proposal can provide empirical data to reconcile strictly localizationalist vs. distributionist accounts of brain function. Relevant to th NIH mission, the neural mechanisms underlying brain plasticity identified in the proposed studies can serve as targets for the development of diagnostic biomarkers as well as cognitive therapy interventions for rehabilitation of patients with brain damage from prevalent neurological disorders such as stroke and traumatic brain injury.